OP0020 SEX DIFFERENCES IN EFFECTIVENESS OF FIRST-LINE TUMOR NECROSIS FACTOR INHIBITORS IN AXIAL SPONDYLOARTHRITIS; RESULTS FROM FIFTEEN COUNTRIES IN THE EuroSpA RESEARCH COLLABORATION NETWORK
Authors: P. Hellamand, M. G. H. Van de Sande, L. Midtbøll Ørnbjerg, T. Klausch, M. Nurmohamed, R. Van Vollenhoven, D. Nordström, A. M. Hokkanen, M. J. Santos, E. Vieira-Sousa, A. G. Loft, B. Glintborg, M. Østergaard, U. Lindström, J. K. Wallman, B. Michelsen, A. Ciurea, M. J. Nissen, C. Codreanu, C. Mogosan, G. Macfarlane, G. T. Jones, K. Laas, Z. Rotar, M. Tomsic, I. Castrejon, M. Pombo-Suarez, B. Gudbjornsson, A. J. Geirsson, E. Kristianslund, J. Vencovský, L. Nekvindova, S. Gulle, B. Zengin, M. L. Hetland, I. Van der Horst-Bruinsma
Journal: Annals of the Rheumatic Diseases (2022)

Background Evidence reveals sex differences in physiology, disease presentation and response to treatment in axial spondyloarthritis (axSpA). Pooled data from four randomized controlled trials demonstrated reduced treatment efficacy of a tumor necrosis factor inhibitor (TNFi) in females compared to males with ankylosing spondylitis 1 . However, real-life evidence confirming these data in large cohorts is scarce. We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice. Objectives To investigate sex differences in treatment response and drug retention rates in clinical practice among patients with axSpA, treated with their first TNFi. Methods Data from biologic-naïve axSpA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on clinically important improvement (CII) according to ASDAS-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on CII. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (&lt;20% missing). The final covariates included in the model were country, age and TNFi start year. In the secondary analysis, drug retention was assessed over 24 months of follow-up by Kaplan-Meier curves and log-rank test. Results In total, 6,451 axSpA patients with available data on ASDAS-CRP at baseline and 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have CII was 15% (RR, 0.85; 95% confidence interval [CI], 0.82 to 0.89) lower compared to males and the difference in probability for having CII was 9.4 percentage points (RD, 0.094; 95% CI, 0.069 to 0.12). The survival analysis included 28,608 axSpA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/69%/58%) compared to males (89%/81%/72%), see Figure 1. Table 1. Female Male Mean (SD), Median [IQR] or percentages Mean (SD), Median [IQR] or percentages Age (years) 42.0 (12.1) 41.4 (12.3) Fulfilment of mNYC 66% 80% Disease duration (years) 2.0 [1.0, 7.0] 3.0 [1.0, 9.0] TNFi start year Start 1999-2009 7.2% 9.8% Start 2010-2013 26% 27% Start 2014-2016 37% 36% Start 2017-2020 30% 27% BASDAI, mm 59 (20) 54 (21) BASFI, mm 48 (25) 46 (24) ASDAS, units 3.5 (0.9) 3.5 (1.0) CRP (mg/L) 6.7 [2.5, 16.0] 11.9 [4.0, 25.0] SJC (0-28) 0 [0, 0] 0 [0, 0] TJC (0-28) 0 [0, 2] 0 [0, 1] VAS pain, mm 63 (22) 59 (24) VAS fatigue, mm 65 (25) 59 (26) mNYC, modified New York criteria; TNFi, tumor necrosis factor inhibitor; BASDAI, Bath Ankylosing Spondylitis Disease Activity Indexf; BASFI, Bath Ankylosing Spondylitis Functional Index; ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale. Conclusion Treatment efficacy and retention rates are lower among female patients with axSpA initiating their first TNFi. Females presented with lower C-reactive protein levels and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education. References [1]van der Horst-Bruinsma et al. Ann Rheum Dis. 2013 Jul;72(7):1221-4. Acknowledgements Novartis Pharma AG and IQVIA for supporting the EuroSpA collaboration. Disclosure of Interests Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Abbvie, Eli Lily, Novartis and UCB, Grant/research support from: Novartis, Janssen, UCB and Eli Lilly, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Thomas Klausch: None declared, Michael Nurmohamed Speakers bureau: Abbvie, Janssen and Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB and speaker fees from Abbvie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB, Grant/research support from: BMS, GSK and UCB, Dan Nordström Consultant of: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Anna-Mari Hokkanen Grant/research support from: MSD, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Elsa Vieira-Sousa Speakers bureau: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Consultant of: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Grant/research support from: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Anne Gitte Loft Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie and BMS, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene and Novartis, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly and Novartis, Brigitte Michelsen Grant/research support from: Novartis, Adrian Ciurea Speakers bureau: AbbVie and Novartis, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Corina Mogosan Speakers bureau: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Gary Macfarlane Grant/research support from: GSK, Gareth T. Jones Grant/research support from: AbbVie, Pfizer, UCB, Amgen and GSK, Karin Laas Speakers bureau: Amgen, Janssen, Novartis and Abbvie, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Isabel Castrejon Speakers bureau: Eli Lilly, BMS, Janssen, MSD and Abbvie, Consultant of: Eli Lilly, BMS, Janssen, MSD and Abbvie, Manuel Pombo-Suarez Consultant of: Abbvie, MSD and Roche, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Consultant of: Amgen and Novartis, Arni Jon Geirsson: None declared, Eirik kristianslund: None declared, Jiří Vencovský Speakers bureau: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Consultant of: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Lucie Nekvindova: None declared, Semih Gulle: None declared, Berrin Zengin: None declared, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB.